title: Evidence for the role of α1A-adrenoceptor subtype in the control of renal haemodynamics in fructose-fed Sprague-Dawley rat.
abstract: OBJECTIVE
  To explore the hypothesis that high fructose intake results in a higher functional contribution of α1A-adrenoceptors and blunts the adrenergically and angiotensin II (Ang II)-induced renal vasoconstriction.
  
  
  METHODS
  Twelve Sprague-Dawley rats received either 20% fructose solution [FFR] or tap water [C] to drink ad libitum for 8 weeks. The renal vasoconstrictor response to noradrenaline (NA), phenylephrine (PE), methoxamine (ME) and Ang II was determined in the presence and absence of 5-methylurapidil (5-MU) (α1A-adrenoceptor antagonist) in a three-phase experiment (pre-drug, low- and high-dose 5-MU). Data, mean ± SEM were analysed by ANOVA or Student's unpaired t-test with significance at P < 0.05.
  
  
  RESULTS
  FFR exhibited insulin resistance (HOMA index), hypertension and significant increases in plasma levels of glucose and insulin. All agonists caused dose-related reductions in cortical blood perfusion that were larger in C than in FFR while the magnitudes of the responses were progressively reduced with increasing doses of 5-MU in both C and FFR. The degree of 5-MU attenuation of the renal cortical vasoconstriction due to NA, ME and Ang II was significantly greater in the FFR compared to C.
  
  
  CONCLUSIONS
  Fructose intake for 8 weeks results in smaller vascular response to adrenergic agonists and Ang II. The α1A-adrenoceptor subtype is the functional subtype that mediates renal cortical vasoconstriction in control rats, and this contribution becomes higher due to fructose feeding.
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia. mdapharm78@yahoo.co.uk
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Abdulla
authors.forename: Munavvar A
authors.initials: MA
authors.lastname: Sattar
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Johns
authors.forename: Nor A
authors.initials: NA
authors.lastname: Abdullah
authors.forename: Md Abdul Hye
authors.initials: MA
authors.lastname: Khan
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D005632:Fructose / Q000008:administration & dosage*; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010656:Phenylephrine; D005632:Fructose; D008729:Methoxamine; D009638:Norepinephrine